Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Expression of the CTLA-4 gene is absolutely required for immune homeostasis, but aspects of its molecular nature remain undefined. In particular, the characterization of the soluble CTLA-4 (sCTLA-4) protein isoform generated by an alternatively spliced mRNA of CTLA4 lacking transmembrane-encoding exon 3 has been hindered by the difficulty in distinguishing it from the transmembrane isoform of CTLA-4, Tm-CTLA-4. In the current study, sCTLA-4 has been analyzed using novel mAbs and polyclonal Abs specific for its unique C-terminal amino acid sequence. We demonstrate that the sCTLA-4 protein is secreted at low levels following the activation of primary human CD4(+) T cells and is increased only rarely in the serum of autoimmune patients. Unexpectedly, during our studies aimed to define the kinetics of sCTLA-4 produced by activated human CD4(+) T cells, we discovered that Tm-CTLA-4 is associated with microvesicles produced by the activated cells. The functional roles of sCTLA-4 and microvesicle-associated Tm-CTLA-4 warrant further investigation, especially as they relate to the multiple mechanisms of action described for the more commonly studied cell-associated Tm-CTLA-4.

Original publication

DOI

10.4049/jimmunol.1303389

Type

Journal article

Journal

J Immunol

Publication Date

15/07/2014

Volume

193

Pages

889 - 900

Keywords

Adult, Animals, Antibodies, Monoclonal, Antibody Specificity, Blotting, Western, CD4-Positive T-Lymphocytes, CTLA-4 Antigen, Cells, Cultured, Cytoplasmic Vesicles, Diabetes Mellitus, Type 1, Female, Graves Disease, HeLa Cells, Humans, Immunoassay, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Microscopy, Immunoelectron, Middle Aged, Protein Isoforms, Solubility, Young Adult